Low splenic iron is characteristic of HFE-associated hemochromatosis

Background:

Non-invasive hepatic iron quantification using magnetic resonance imaging (MRI) is a staging method for patients with known iron overload and a diagnostic tool for the work-up of patients with suspected or unexplained iron overload. The aim of the present study was to assess the utility of spleen iron concentrations for the evaluation of hyperferritinemia.

Methods:

Of all patients with high serum ferritin (≥200 µg/L for women and ≥300 µg/L for men) observed between July 2001 and November 2017, 460 were HFE genotyped and underwent non-invasive liver and spleen iron quantification by T2* weighted MRI. After exclusion of 50 patients with a history of phlebotomy in the year prior to inclusion, clinical, biochemical and radiological data of 410 patients were retrospectively analysed. The degree of iron content is expressed as R2* (= 1/T2*).

Results:

Forty-one patients were homozygous for the p.C282Y mutation in the HFE gene. When the latter were compared to patients with all other genotypes, median R2* was significantly higher in the liver but also significantly lower in the spleen. Median transferrin saturation was significantly higher in the p.C282Y homozygous group. Patient groups did not differ in terms of age or serum ferritin.

Conclusion:

High ferritin is a common clinical finding that can indicate iron overload, inflammation and cell death. Our study shows that p.C282Y homozygous patients have significantly higher hepatic iron. In accordance with the low hepcidin state of hemochromatosis, reduced splenic iron concentrations in this condition indicate uncontrolled iron release and high transferrin saturation. Splenic iron can therefore be used to guide genetic testing beyond HFE genotyping, where patients with high liver but low spleen iron should preferably be tested for non-HFE mutations.

Tab. 1:

Clinical, biochemical and radiological data. Median values are represented and the 25th and 75th percentiles are given between parentheses.

	p.C282Y homozygous (n = 41)	all other HFE genotypes (n = 369)	P value
Age, years	53 (40 – 63)	53 (44 – 64)	0.29
BMI, kg/m2	25.2 (22.8 – 26.9)*	26.9 (23.9 – 29.7)	0.02
Serum iron, µmol/L	36.2 (28.3 – 41.4)	21.9 (17.5 – 28.3)	< 0.001
Serum ferritin, µg/L	722 (422 – 1470)	696 (503 – 1075)	0.70
Transferrin, mg/dL	201 (181 – 211)	240 (212 – 266)	< 0.001
Transferrin saturation, %	77 (62 – 83)	36 (28 – 47)	< 0.001
Alanine aminotransferase, U/L	29 (25 – 56)	40 (26 – 66)	0.15
R2* liver, s-1	207.3 (124.4 – 335.9)	72.1 (57.0 – 100.7)	< 0.001
R2* spleen, s-1	38.6 (31.8 – 54.6)	49.2 (37.8 – 66.3)	0.007
Liver R2*/spleen R2* ratio	4.9 (3.4 – 6.8)	1.5 (1.1 – 2.2)	< 0.001